118332-07-3Relevant articles and documents
Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase
Hinman, Andrew,Holst, Charles R.,Latham, Joey C.,Bruegger, Joel J.,Ulas, G?zde,McCusker, Kevin P.,Amagata, Akiko,Davis, Dana,Hoff, Kevin G.,Kahn-Kirby, Amanda H.,Kim, Virna,Kosaka, Yuko,Lee, Edgar,Malone, Stephanie A.,Mei, Janet J.,Richards, Steve James,Rivera, Veronica,Miller, Guy,Trimmer, Jeffrey K.,Shrader, William D.
, (2018/09/27)
Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.
